Transvenous Optoacoustic-Ultrasound Guided Cold Laser Wire for Crossing Coronary Chronic Total Occlusion

摘要 冠状动脉慢性完全闭塞(CTO)是由硬纤维钙化物质组成的动脉粥样硬化斑块。 这会100%限制管腔横截面，导致受影响动脉的血流完全停止 至少三个月。CTO症状包括呼吸急促并伴有慢性疲劳和胸痛。这个 CTO的三种主要治疗方案是药物疗法(MT)、冠状动脉旁路移植术(CABG)和 经皮冠状动脉介入治疗(PCI)。MT可以减轻胸痛等症状，但不能解决 潜在的疾病机制。冠状动脉旁路移植术确实显著改善了患者的发病率和 然而，这种心内直视手术治疗具有高度侵入性、创伤性、费用昂贵和治疗效果有限的特点。 一辈子。由于大多数冠状动脉旁路移植术使用的是再利用的静脉，50%的冠状动脉旁路移植术后10年内闭塞。 心脏搭桥手术。PCI程序提供24小时以上的住院时间，有一到两天的恢复时间 费用约占冠脉搭桥术的四分之一，但目前只有10%的CTO患者接受了治疗。在 最常见的经皮冠状动脉介入治疗是血管内膜下穿透，机械钢丝穿过血管内的CTO。 墙。很少有干预者实行内膜下穿刺术，因为这一过程难度大、风险大且相关。 有较高的MACE、再狭窄、急性心肌梗死和死亡。尽管已经引入了许多血管内装置 在进行经皮冠状动脉腔内CTO穿刺术时，冠状动脉均失败。这些以前的失败 导管堵塞的原因至少有三种：1)导管直径太大，太硬，可操纵性差； 2)CTO切割对血管壁造成的非特异性损伤；3)缺乏导航指导 该系统基于导管尖端相对于动脉壁的实时成像。一种光声(OA)和 超声(US)图像引导的冷激光丝(CLW)被提出，它提供受控切割，将允许 任何介入心脏病专家为患者提供安全有效的经皮冠状动脉腔内CTO穿刺术。 经静脉OA/US影像引导CLW的开发将通过完成三个特定的 目标：目标1：研制光声/超声经静脉图像引导冷激光器 导线；目标2：在体外人冠状动脉搭桥术心脏中测试CLW True-Lumen PCI CTO交叉；目标3：测试CLW 活体动物模型中钙化CTO的真管腔经皮冠状动脉介入治疗。圆满完成 拟议的研究和开发计划将引入真正管腔的PCI CTO交叉程序，该程序 当支架植入后，可以为介入性心脏病学建立一种优越的新治疗范例 并可能影响其他外科学科。

ABSTRACT Coronary chronic total occlusions (CTOs) are atherosclerotic plaques comprised of hard fibro-calcific material that restrict luminal cross-section by 100% resulting in complete stoppage of blood flow in the affected artery for at least three months. CTO symptoms include shortness of breath with chronic fatigue and chest pain. The three primary CTO treatment regimens are medical therapy (MT), coronary artery bypass graft (CABG) and percutaneous coronary interventions (PCI). MT can reduce symptoms such as chest pain but fail to address the underlying disease mechanisms. CABG does provide marked improvements in both patient morbidity and mortality, however, this open-heart surgical intervention is highly invasive, traumatic, expensive and has a limited lifetime. Because most CABG grafts utilize re-purposed veins, 50% become occluded within ten years after bypass surgery. PCI procedures are provided over a 24-hour hospital stay, have one-two days of recovery time and cost approximately one-fourth of CABG yet are currently administered to only 10% of CTO patients. In the most common PCI procedure, subintimal crossing, a mechanical wire is advanced past the CTO inside the vessel wall. Few interventionalists practice subintimal crossing because the procedure is difficult, risky and associated with higher MACE, restenosis, acute MI and death. Although many intravascular devices have been introduced to perform PCI true-lumen CTO crossing, all have failed in the coronary arteries. Failure of these previous devices is due to at least one of three causes: 1) large-diameter catheters that are too rigid with poor steerability; 2) non-specific injury to the vessel wall resulting from CTO cutting; and 3) absence of a navigational guidance system based on real-time imaging of the catheter tip relative to the arterial wall. An optoacoustic (OA) and ultrasound (US) image-guided cold laser wire (CLW) is proposed that provides controlled cutting that will allow any interventional cardiologist to provide patients safe and efficacious PCI true-lumen CTO crossing. Development of the transvenous OA/US image-guided CLW will be accomplished by completing three specific aims: Aim 1: Develop an Optoacoustic (OA)/Ultrasound (US) Transvenous Image-Guided Cold Laser Wire; Aim 2: Test CLW True-Lumen PCI CTO Crossing in ex vivo Human CABG Hearts; Aim 3: Test CLW True-Lumen PCI Crossing of Calcified CTOs in in vivo Animal Models. Successful completion of the proposed research and development program will introduce a true-lumen PCI CTO crossing procedure that when followed by stenting can establish a superior and new treatment paradigm for interventional cardiology and can impact other surgical disciplines.